Phase Diluent Research Articles

Determination of label efficiency and label degree of critical reagents by LC-MS and native MS

Degree of labeling and label efficiency are key factors for optimal characterization of critical reagents that are used in ligand binding assays. Here, three case studies are shown demonstrating how liquid chromatography–mass spectrometry (LC-MS) was utilized to characterize critical reagents using three unique methodologies. Critical reagent batches were prepared for LC-MS analysis by use of: 20 mM dithiothreitol (DTT) (Case 1), rapid PNGaseF (Case 2), and a mobile phase diluent (Case 3). LC-MS was run at three different MS method conditions in each troubleshooting case specific for reduced IgG, intact IgG, and native LC-MS, respectively. Specified LC-MS methods based on sample type and configuration elucidated clear MS profiles, allowing for degree of labeling and label efficiencies to be calculated. Ultimately the LC-MS analyses were fine-tuned for critical reagent characterization, and practices for analyzing similar reagents in the future can be established.

Diluent effects in the solvent extraction of rhenium (VII) with amine extractants in [Tf2N]-based ionic liquids: Experimental and COSMO-RS analysis

In this work, the factors that determine a high or low extraction performance when using ionic liquids (ILs) as diluents in the solvent extraction of Rhenium (Re(VII)) from aqueous solutions were studied by means of experiments, quantum chemical (QC) calculations, and COSMO-RS. For this purpose, kerosene and the ionic liquids (ILs) 1-butyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide [C4C1im][Tf2N], or 1-methyl-3-octylimidazolium bis(trifluoromethylsulfonyl)imide [C8C1im][Tf2N] were used as diluents to determine de effect of alkyl chain of ILs, and two high molecular weight amines: trioctylamine (TOA) and Alamine 336 (Al336) were used as the extractants. The results indicated that the so-called reference extracting phase TOA in kerosene achieved 99% extraction percentages. On the contrary, a lower performance was observed when replacing kerosene with any of both ILs. This reduction was mainly due to two reasons. First, the IL dissociates where the cation takes part in the formed complex, hindering the TOA-perrhenate bonding, and second, the formed complex that contains IL cations shows poor dissolution in the diluent phase. This could be avoided by means of long alkyl chain imidazolium bis(trifluoromethylsulfonyl)imide-based ILs. Additionally, operating parameters such as equilibrium stages and concentration of the stripping agent were studied. Promising results were obtained by replacing TOA with Al336 dissolved in the IL [C8C1im][Tf2N], showing very similar results with the reference extracting phase.

Alkali Metal Ion Partitioning with Calix[4]arene-benzo-crown-6 Ionophore in Acidic Medium: Insights from Experiments, Statistical Mechanical Framework, and Molecular Dynamics Simulations.

The current work reports the experimental and predicted interfacial behavior of metal ion extraction from aqueous phase-diluent system using a newly synthesized calix-benzo-crown-6 (CBCBGA) ionophore. Conductor-like screening model for real solvents was used to predict the selectivity at infinite dilution for the metal ion complexes in both aqueous and diluent phases. The selectivity for Cs+-CBCBGA extraction was found to be higher than that of other metal ions, namely, K+, Na+, and Rb+. This was confirmed by the experimental distribution coefficients obtained in the diluents system at 3 M HNO3 along with 0.01 M CBCBGA/organic solvents. The high selectivity of Cs+-CBCBGA complex over other complexes (K+, Rb+, and Na+) in nitrobenzene was also confirmed and validated by the highest occupied molecular orbital-lowest unoccupied molecular orbital energy gap (i.e., 0.13114 > 0.12411 > 0.11719 > 0.11561 eV) and interaction energy (i.e., -68.25 > -57.11 > -55.52 > -52.37 kcal/mol). The interaction and free energies of the extraction were found to increase with the dielectric constant of the organic solvents, namely, nitrobenzene > o-nitrophenyl hexyl ether > 1-octanol > chloroform. Overall, a higher selectivity of Cs+ ion over that of other metal ions (K+, Na+, and Rb+) was obtained for the newly synthesized CBCBGA ionophore in a radioactive waste solution.

RECOVERY OF FORMIC ACID BY REACTIVE EXTRACTION USING AN ENVIRONMENTALLY-FRIENDLY SOLVENT

Today many carboxylic acids are recovered from biological production media and industrial wastewaters. Reactive extraction is favored over other separation methods due to its high recovery efficiency, ease of operation, low energy demand and reduced cost. However, use of toxic organic diluents in the organic phases is the main disadvantage of the method. In this study, the appropriateness of an environmentally-friendly solvent, sunflower oil (SFO) to be used as organic phase diluent during the recovery of formic acid (FA) from aqueous solutions by reactive extraction was evaluated. Alamine-336 was used as the extractant and the results obtained with SFO were compared with those obtained using octanol. The separation process reached an equilibrium in 3 hours and the recovery efficiency increased with the increase in extractant percentages. The initial FA concentration positively influenced the recovery when SFO was used as the diluent. In the ranges of the parameters studied, the highest recovery values were 98.6% and 82.6% with octanol and SFO, respectively. This study shows that low molecular weight carboxylic acids, e.g. FA can be recovered from aqueous solutions by reactive extraction using environmentally-friendly solvents such as SFO.

Comparison of supercritical fluid chromatography and reverse phase liquid chromatography for the impurity profiling of the antiretroviral drugs lamivudine/BMS-986001/efavirenz in a combination tablet

Dual and triple combinations of antiretroviral drugs are a cornerstone of human immunodeficiency virus type 1 (HIV-1) treatment. Supercritical fluid chromatography (SFC) and reverse phase liquid chromatography (RPLC) methods have been developed for the impurity profiling of a prototype combination tablet containing three such drugs: lamivudine, BMS-986001 and efavirenz. Separation by SFC was achieved using a Princeton 2-ethyl pyridine stationary phase and a mobile phase B consisting of methanol with 10mM ammonium acetate and 0.1% isopropyl amine. This combination of mobile phase additives was required for both the separation of minor components and to minimize peak tailing of the active pharmaceutical ingredients (APIs). Separation by RPLC was achieved using a Discovery HSF5 stationary phase and a mobile phase consisting of 10mM ammonium acetate, pH 5.5 and methanol. Mobile phase gradient elution was employed in each case to elute components with a wide range of polarities. Both these methods were found to have advantages and disadvantages. Out of the three APIs and 13 possible impurity/degradation products selected, all were resolved by RPLC. By SFC, 15 peaks were resolved with one co-eluting pair and a high degree of orthogonality was achieved relative to RPLC. A more even distribution of peaks across the separation space, a non-sloping baseline and fewer system peaks were significant advantages associated with the SFC method. Particular attention had to be paid to optimizing the reverse phase diluent strength/initial mobile phase composition to avoid distortion of the peak shapes for early eluting components. This was not an issue with SFC, as the diluent of choice (methanol) was also the solvent of choice (in combination with ≤20% water) for the dissolution of the triple combination tablet. As with RPLC, SFC was found to exhibit the required sensitivity for successful quantitation of potential impurities/degradation products at the 0.05–0.1 area% level.

Extraction of cadmium bromide and picrate by 18-crown-6 ether into various less-polar diluents: Analysis of overall extraction equilibria based on their component equilibria with formation of their ion pairs in water

Extraction constants (Kex and Kex±) of CdBr2 into eleven diluents and Cd (Pic)2 into eight diluents by 18-crown-6 ether (18C6) and apparent distribution constants (KD,A) of pairing anions (A−) were determined at 25°C. Here, Kex, Kex±, and KD,A were defined as [CdLA2]o/[Cd2+][L]o[A−]2, [CdLA+]o[A−]o/[Cd2+][L]o[A−]2, and [A−]o/[A−], respectively; L=18C6, A−=Br− and picrate ion (Pic−), and the subscript “o” denotes the diluent phase. Also, K2org was estimated from the ratio Kex/Kex±. Using the two extraction constants and their component equilibrium ones, extraction-abilities and -selectivities of the diluents for the above extraction systems were discussed. From the KD,A values, the distribution constants of cationic ion-pairs CdLA+ into 1,2-dichloroethane (DCE) and dichloromethane (DCM) were also standardized and thereby ion-transfer potentials of CdLA+ at water (w)/DCE and w/DCM interfaces were estimated. Further, interactions of neutral ion-pairs CdLA2 with w molecules were examined with cohesive energy densities obtained from the plots of log Kex,ipversus log KD,L, where Kex,ip and KD,L denote an ion-pair extraction constant of CdLA2 into the diluents and the distribution one of 18C6, respectively.

Ethyl-bis-triazinylpyridine (Et-BTP) for the separation of americium(III) from trivalent lanthanides using solvent extraction and supported liquid membrane methods

The present paper deals with the solvent extraction and supported liquid membrane studies on Ln(III)/An(III) separation using ethyl-bis-triazinylpyridine (Et-BTP) as the extractant. The solvent extraction studies involved evaluation of a) diluents, b) phase modifiers, c) stripping agents and d) role of feed acidity. Though reasonably high separation factor values were obtained when Et-BTP was used along with α-bromo carboxylic acids, the mixtures could not be used for liquid membrane studies due to unsatisfactory stripping. On the other hand, a combination of Et-BTP with chlorinated cobalt dicarbollide (CCD) in nitrobenzene resulted in significant Am(III) mass transfer when used in the solvent extraction as well as SLM studies. Improved transport, membrane stability, and decontamination from lanthanides were observed when the organic phase diluent composition was 60% nitrobenzene + 40% n-dodecane. Using 0.02 M Et-BTP along with 0.005 M CCD in 60% nitrobenzene + 40% n-dodecane, the SLM studies on a mixture of 241Am, 152Eu and 147Nd in a feed containing 0.1 M HNO 3, indicated quantitative Am 3+ transport in 3.5 h with co-transport of about 8% Nd 3+ and 22% Eu 3+.

The role of the diluent phase in the mechanochemical preparation of TiO 2 nanoparticles

Anatase and rutile TiO 2 nanoparticles were synthesized via mechanochemical reaction and subsequent annealing of the products. TiO 2 nanoparticles were prepared by the use of planetary ball milling of titanyl sulphate (TiOSO 4. xH 2O. yH 2SO 4) and NaCl powders as the reactant and diluent phases, respectively. In this paper, the effect of volume fraction of diluent phase (NaCl) on the particle size distribution and agglomeration of TiO 2 nanoparticles is studied. Final products were obtained by annealing the milled powders at 700 °C for half an hour and subsequent washing out the water-soluble NaCl. X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) investigations showed that the increase in NaCl:TiOSO 4 weight ratio (NTR) leads to the formation of nanocrystalline anatase and rutile particles with more uniform size distribution, lower weight ratio of rutile phase and lower agglomeration of particles.

EFFECT OF MILLING TIME ON MECHANOCHEMICAL SYNTHESIS OF TiO2 NANOPARTICLES

Titanium dioxide nanoparticles have great potential for use in photocatalytic applications, cosmetics, white pigments and so on. In this paper, the effect of milling time on particle size, morphology and phase composition of TiO 2 nanoparticles, prepared by mechanochemical method, was investigated by X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). TiO 2 nanoparticles were prepared by the use of high energy ball milling of titanyl sulphate ( TiOSO 4) and NaCl powders as the starting mixture in different milling durations. The milled powder was annealed at 700°C for 30 min. The NaCl powder, used as the diluent phase, was removed by washing the annealed powder with distilled water. It was found that with increasing milling time, decrease in the size of equiaxed spherical particles and increase in temperature of anatase to rutile transformation ( A → R ) can be observed.

Membrane extraction for removal of acetic acid from biomass hydrolysates

Production of bioethanol from lignocellulosic biomass requires pretreatment of the biomass in order to improve the susceptibility of the cellulose to enzymatic hydrolysis to glucose. When dilute acid is used to perform this process, the hemicellulose is also hydrolyzed to its component sugars while simultaneously releasing acetyl groups attached to the hemicellulose backbone. Other compounds from the lignin and sugar degradation products are also produced that inhibit subsequent bioconversion of the solubilized sugars to the desired products. In this work we focused on removal of acetic acid from a dilute sulphuric acid pretreated corn stover hydrolysate. Acetic acid has been extracted into an organic phase at pH values below its p K a. The organic phase diluent consisted of octanol. Alamine 336, a tertiary amine and Aliquat 336 a quaternary amine were used as the aliphatic amine extractants. Our results indicate more than 60% removal of acetic acid using Alamine 336. Extraction rates were much slower for Aliquat 336 probably due to the higher viscosity of the Aliquat 336/octanol phase. The presence of sulphate anions, as a result of dilute sulphuric acid pretreatment, results in the co-extraction of bisulphate anion. Bisulphate anion is preferentially extracted at pH values below its p K a. Consequently the pH of the hydrolysate increases from between 1 and 2 to above 4.0 during extraction. In addition, extraction of low molecular weight lignins and phenolics is also observed. Thus the membrane extraction process developed here may be used not only for removal of acetic acid but also to adjust the pH of the hydrolysate to values that are more compatible for fermentation and to remove other inhibitory compounds.

Synthesis of TiO2 nanoparticles via a novel mechanochemical method

Abstract A novel preparation method for titanium dioxide (TiO2) nanoparticles is introduced in this paper. In this process, titanyl sulphate (TiOSO4·xH2SO4·yH2O) and NaCl powders were used as the reactant and diluent phases, respectively. In order to understand the thermal behavior of the reactant, thermo-gravimetric analysis/differential thermo-gravimetry (TGA/DTG) was conducted. The starting mixture of the reactant and NaCl powders were loaded into a planetary ball mill, under argon atmosphere at 400 rpm. The final products were obtained by annealing the milled powders in the temperature range of 600–900 °C and subsequently by washing out the water-soluble NaCl. Scanning electron microscopy (SEM) investigations showed that nanosized titania particles have equiaxed shape with the mean size in the range of 15–50 nm. Mechanism of the formation of TiO2 during milling was studied via Fourier transform infrared (FTIR) spectroscopy.

Selective separation of silver(I) by novel substituted thiourea

The extraction of silver(I) from nitric acid solutions using naphthyl substituted thiourea such as 1-naphthylthiourea (ANTU) has been studied. Different variables: equilibration time, aqueous pH, chloride and extractant concentrations and organic phase diluent that could affect the extraction system were evaluated at 28.0 ± 2.0 °C. It was found that silver is quantitatively extractred by ANTU over the entire studied range of nitric acid concentration. Extraction of silver by ANTU is fast and equilibration was achieved in less than five minutes. Experimental data relating to silver have been analysed to determine the stoichiometry of the extracted species. Effect of foreign ions on the extraction of silver was carried out. Recycling capacity of the extractant was also studied. Thiourea and EDTA solutions were found suitable for > 99% stripping of extracted silver(I). The reagent has been found to have high selectivity for silver against copper, cadmium, nickle, cobalt, halfnium, zircomium and europium.

Carrier-facilitated transport of Cd(II) from a high-salinity chloride medium across a supported liquid membrane containing Cyanex 923 in Solvesso 100

The transport of cadmium (II) from a high-salinity chloride medium across a flat-sheet supported liquid membrane containing Cyanex 923 in Solvesso 100 supported on a PVDF membrane into a strip solution with water was investigated. Permeability coefficients of metal increased with decreasing the pH of feed from 2.0 to 0.5. It also increases with increasing carrier concentration in the membrane phase, whereas the permeation is dependent on the organic phase diluent but independent of metal concentration in the feed phase. The performance of the present system against other carriers was also studied.

Effect of the polypropylene type on polymer–diluent phase diagrams and membrane structure in membranes formed via the TIPS process: Part I. Metallocene and Ziegler–Natta polypropylenes

Isotactic polypropylene (iPP) samples produced via Ziegler–Natta catalysts (iPPZN) and metallocene catalysts (iPPM) were used to investigate the effects of molecular weight and molecular weight distribution on the phase diagram for iPP–diphenyl ether systems and the morphology of membranes made from these systems. It was found experimentally that the molecular weight and molecular weight distribution influenced the location of the cloud point curve and the morphology of membranes produced via thermally induced phase separation. The influence on the cloud point curve was attributed to entropic and enthalpic considerations. The influence on membrane morphology was attributed to differences in the growth period (resulting from a shift in the cloud point and dynamic crystallization curves) and differences in system viscosity. All of these factors are related to the type of catalyst used to produce the iPP.

Effect of the polypropylene type on polymer–diluent phase diagrams and membrane structure in membranes formed via the TIPS process: Part II. Syndiotactic and isotactic polypropylenes produced using metallocene catalysts

Syndiotactic polypropylene (sPP) and isotactic polypropylene (iPP) were used to investigate the effect of the polypropylene microstructure (tacticity) on phase diagrams for PP–diphenyl ether systems and the morphology of membranes made from these systems. The syndiotactic and isotactic polypropylenes were both produced via metallocene catalysts and had similar average molecular weights. It was found experimentally that polypropylene microstructure affects the location of the binodal curve and the morphology of membranes produced via the thermally induced phase separation (TIPS) process. The influence on the binodal curve was attributed to stereochemistry effects, chain rigidity, and local chain packing. In isothermal experiments, droplet size was similar for the two types of PP, while in non-isothermal experiments, the sPP sample yielded larger droplets than the iPP sample. These results were attributed mainly to viscous effects and to differences in the growth period (resulting from a shift in the cloud point and dynamic crystallization curves). The final morphology of the sPP membrane was related to polymer chain flexibility and to shrinkage of the sample during diphenyl ether extraction and sample drying.

Uniform Particles for the Reversed-Phase Separation of Proteins with High-Resolution and High-Column Efficiency

A low‐sized, uniform and polymer‐based high‐performance liquid chromatography (HPLC) packing material capable of making reversed‐phase separation of proteins with high resolution and with high column efficiency was developed. By a multistage‐swelling and polymerization protocol, 5 µm‐uniform‐porous poly(styrene‐co‐divinylbenzene) particles with relatively larger pores particularly suitable for protein separation were synthesized by starting from a low‐sized seed latex with high average molecular weight and by using a diluent phase comprised of dibutylphthalate and toluene. By the use of synthesized beads as packing material in HPLC, high‐resolution liquid chromatograms were obtained in the gradient separation of selected proteins (i.e., ribonuclease‐A, lysozyme, cytochrome C, and albumin). In the chromatographic runs, the flow rate of the mobile phase was increased fourfold by preserving the resolution power of the column material under gradient conditions. The theoretical plate numbers (TPN) up to 12.500 plates/m were observed by using cytochrome C as the analyte. TPN values determined by the proteins were significantly higher relative to the similar uniform packing materials larger in size (i.e., 7.5–10 µm) obtained by different polymerization methods.

The phosphine oxides Cyanex 921 and Cyanex 923 as carriers for facilitated transport of chromium (VI)-chloride aqueous solutions

The behaviour of the phosphine oxides Cyanex 921 and Cyanex 923 in the facilitated transport of chromium (VI) from chloride solutions is described. Transport is studied as a function of several variables such as stirring speeds of the aqueous phases, membrane phase diluent, hydrochloric acid concentration in the source phase and chromium and carrier concentrations. The separation of chromium (VI) from other metals presented in the source phase as well as the behaviour of phosphine oxides with respect to other neutral organophosphorous derivatives (tri- n-butylphosphate (TBP) and dibutyl butylphosphonate (DBBP)) are also investigated. Moreover, by using hydrazine sulphate in the receiving phase, Cr(VI) is immediately reduced to the less toxic Cr(III).

Solvent extraction of silver by LIX® 79: experimental equilibrium study

The extraction of silver(I) from argentocyanide aqueous cyanide solutions using LIX® 79 has been studied. Different variables that could affect the extraction system were evaluated: equilibration time, aqueous pH, metal and extractant concentrations, and organic phase diluent. The extraction of the Ag(CN)2− complex with respect to other metal-cyano complexes has also been studied on both synthetic and real leach solutions. Experimental data relating to silver have been analysed numerically to determine the stoichiometry of the extracted species and its equilibrium constant. It was found that silver(I) was extracted into the organic phase by the formation of the species RHAg(CN)2 (LIX 79 = R). Copyright © 2004 Society of Chemical Industry

The effects of viscosity on coalescence-induced coalescence

The effects of variable matrix-phase viscosity on the rate of coarsening of relatively inviscid diluent droplets in a viscous polymer matrix are examined. Emulsions of low viscosity diphenyl ether (DPE) droplets in a viscous matrix mixture of isotactic polypropylene (iPP) and DPE are formed by thermal quenching of a homogeneous phase below the binodal. The droplets coarsen via the mechanism of coalescence-induced coalescence (CIC), where two coalescing droplets create a flow that drives other droplets to coalesce, thus creating a cascade process. Previous work on CIC indicate that the growth exponent of the average droplet size depends on the volume fraction of the diluent phase, but does not depend on the viscosity of the matrix phase or the DPE–iPP interfacial tension. Different iPP molecular weights in the experiments cause a variation in the viscosity, but practically no change in the interfacial tension nor in the phase behavior of the system. The growth exponent is found to not vary with the viscosity of the matrix phase, supporting the CIC theory.

The phosphine oxides Cyanex 921 and Cyanex 923 as carriers for facilitated transport of gold(I) cyanide aqueous solutions

The behaviour of the phosphine oxides Cyanex 921 and Cyanex 923 in the facilitated transport of gold(I) from cyanide solutions is described. Transport is studied as a function of several variables such as stirring speeds of the aqueous phases, membrane phase diluent, pH of the source phase, ionic strength, and gold and carrier concentrations. The separation of the gold(I) cyanide complex from other metal-cyano complexes present in the source phase as well as the behaviour of phosphine oxides with respect to other neutral organophosphorous derivatives (tri- n-butylphosphate (TBP) and dibutyl butylphosphonate (DBBP)) are also investigated.